AB0144 PD-1 DEFICIENCY IN THE REGULATORY T CELL MAY BE INVOLVED IN THE PATHOGENESIS IN TAKAYASU’S ARTERITIS
Authors: N. Gaon, L. Pan
Journal: Annals of the Rheumatic Diseases (2022)

Background Regulatory T cell (Treg cell) has been demonstrated decreased in peripheral blood of TAK patients in recent researches. PD-1 may regulate Treg cell differentiation and apoptosis as an important checkpoint molecule. Objectives This study aims to investigate whether PD-1 is involved in the abnormal of Treg cell in TAK. Methods This study enrolled 49 patients with TAK and 23 healthy controls. Treg cell related serum cytokines IL-10, IL-7, IL-2 and IL-15, as well as serum chemokines CCL2, CCL3 and CXCL10 were detected using cytokine cytometric bead array. The expression of PD-1 in CD4 + Foxp3 - T cells and Treg cells were analyzed by flow cytometry analysis in 15 patients with TAK and 18 healthy controls. Results Mean fluorescence intensity of PD-1 in CD4 + PD-1 + cells decreased in TAK patients [72.2 (45.8, 84.7) vs. 363.00(335, 431), P = 0.000]. The frequency of CD4 + Foxp3 - PD-1 + cells in CD4 + T cells decreased in peripheral blood（9.05 ± 1.06% vs. 12.61 ± 1.17%，P = 0.034）of TAK patients. The percentage of CD4 + CD25 + Foxp3 + PD-1 + cells in CD4 + CD25 + T cells（0.40 ± 0.05% vs. 0.63 ± 0.09%，P = 0.047）is lower in TAK patients than healthy controls. Higher serum levels of IL-10[4.84（0.07,409.57）vs.3.16（0,69.15）, P = 0.004] and IL-7[10.05（2.68,227.2）vs. 7.4（2.68,16.77）, P = 0.014] level were observed in TAK patients. Compared to healthy controls, serum CCL2[30.64（0，686.84）vs. 10.31（0，32.92），P = 0.000] and CCL3[3.01(0.69,19.24)vs.1.84（0.87，4.6），P = 0.000] increased obviously. Conclusion The frequency of CD4 + Foxp3 - PD-1 + /CD4 + T cells and CD4 + CD25 + Foxp3 + PD-1 + /CD4 + CD25 + T cells decreased. This study suggested that PD-1 may contribute to the imbalance of regulatory T cell in TAK. References [1]Tombetti E, Mason JC. Takayasu arteritis: advanced understanding is leading to new horizons. Rheumatology (Oxford). 2019;58(2):206–219. [2]Gao N, Cui W, Zhao LM, Li TT, Zhang JH, Pan LL. Contribution of Th2-like Treg cells to the pathogenesis of Takayasu’s arteritis. Clin Exp Rheumatol. 2020; 38 Suppl 124(2):48-54. [3]Patsoukis N, Wang Q, Strauss L, Boussiotis VA. Revisiting the PD-1 pathway. Sci Adv. 2020;6(38):eabd2712. [4]Zhang S, Wang L, Li M, Zhang F, Zeng X. The PD-1/PD-L pathway in rheumatic diseases. J Formos Med Assoc. 2021;120(1):48-59. [5]Le Burel S, Champiat S, Routier E, Aspeslagh S, Albiges L, Szwebel TA, et al. Onset of connective tissue disease following anti-PD1/PD-L1 cancer immunotherapy. Ann Rheum Dis. 2018;77(3):468–470. [6]Daxini A, Cronin K, Sreih AG. Vasculitis associated with immune checkpoint inhibitors-a systematic review. Clin Rheumatol. 2018;37(9):2579–2584. [7]Zhang H, Watanabe R, Berry GJ, Vaglio A, Liao YJ, Warrington KJ, et al. Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis. Proc Natl Acad Sci U S A. 2017;114(6):E970–E979. [8]Kermani TA. Takayasu arteritis and giant cell arteritis: are they a spectrum of the same disease? Int J Rheum Dis. 2019;22 Suppl 1:41–48. [9]Kong X, Sun Y, Ma L, Chen H, Wei L, Wu W, et al. The critical role of IL-6 in the pathogenesis of Takayasu arteritis. Clin Exp Rheumatol. 2016;34(3 Suppl 97):S21–S27. [10]Samson M, Bonnotte B. Pathogenesis of large vessel vasculitis. Rev Med Interne. 2016;37(4):264–273. [11]Rosenzwajg M, Lorenzon R, Cacoub P, Pham HP, Pitoiset F, El Soufi K, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019;78(2):209–217. [12]Saraiva M, Vieira P, O’Garra A. Biology and therapeutic potential of interleukin-10. J Exp Med. 2020;6;217(1):e20190418. [13]Barata JT, Durum SK, Seddon B. Flip the coin: IL-7 and IL-7R in health and disease. Nat Immunol. 2019;20(12):1584-1593. [14]Luo CT, Liao W, Dadi S, Toure A, Li MO. Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity. Nature. 2016;28;529(7587):532-6. [15]Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158–168. doi:10.1056/NEJMra1703481. Disclosure of Interests None declared